当前位置:
X-MOL 学术
›
Nat. Commun.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy.
Nature Communications ( IF 14.7 ) Pub Date : 2016-Mar-29 , DOI: 10.1038/ncomms11074
Tamer M A Mohamed 1, 2, 3 , Riham Abou-Leisa 1 , Nicholas Stafford 1 , Arfa Maqsood 1 , Min Zi 1 , Sukhpal Prehar 1 , Florence Baudoin-Stanley 1 , Xin Wang 4 , Ludwig Neyses 1 , Elizabeth J Cartwright 1 , Delvac Oceandy 1
Nature Communications ( IF 14.7 ) Pub Date : 2016-Mar-29 , DOI: 10.1038/ncomms11074
Tamer M A Mohamed 1, 2, 3 , Riham Abou-Leisa 1 , Nicholas Stafford 1 , Arfa Maqsood 1 , Min Zi 1 , Sukhpal Prehar 1 , Florence Baudoin-Stanley 1 , Xin Wang 4 , Ludwig Neyses 1 , Elizabeth J Cartwright 1 , Delvac Oceandy 1
Affiliation
![]() |
The heart responds to pathological overload through myocyte hypertrophy. Here we show that this response is regulated by cardiac fibroblasts via a paracrine mechanism involving plasma membrane calcium ATPase 4 (PMCA4). Pmca4 deletion in mice, both systemically and specifically in fibroblasts, reduces the hypertrophic response to pressure overload; however, knocking out Pmca4 specifically in cardiomyocytes does not produce this effect. Mechanistically, cardiac fibroblasts lacking PMCA4 produce higher levels of secreted frizzled related protein 2 (sFRP2), which inhibits the hypertrophic response in neighbouring cardiomyocytes. Furthermore, we show that treatment with the PMCA4 inhibitor aurintricarboxylic acid (ATA) inhibits and reverses cardiac hypertrophy induced by pressure overload in mice. Our results reveal that PMCA4 regulates the development of cardiac hypertrophy and provide proof of principle for a therapeutic approach to treat this condition.
中文翻译:
心脏成纤维细胞中的质膜钙 ATPase 4 信号传导介导心肌细胞肥大。
心脏通过肌细胞肥大对病理性超负荷作出反应。在这里,我们表明这种反应是由心脏成纤维细胞通过涉及质膜钙 ATP 酶 4 (PMCA4) 的旁分泌机制调节的。小鼠中的 Pmca4 缺失,无论是全身性的还是特异性地成纤维细胞中的缺失,都会降低对压力过载的肥大反应;然而,在心肌细胞中特异性敲除 Pmca4 不会产生这种效果。从机制上讲,缺乏 PMCA4 的心脏成纤维细胞会产生更高水平的分泌型卷曲相关蛋白 2 (sFRP2),从而抑制邻近心肌细胞的肥大反应。此外,我们表明用 PMCA4 抑制剂金精三羧酸 (ATA) 治疗可抑制和逆转由压力超负荷引起的小鼠心脏肥大。
更新日期:2016-04-01
中文翻译:

心脏成纤维细胞中的质膜钙 ATPase 4 信号传导介导心肌细胞肥大。
心脏通过肌细胞肥大对病理性超负荷作出反应。在这里,我们表明这种反应是由心脏成纤维细胞通过涉及质膜钙 ATP 酶 4 (PMCA4) 的旁分泌机制调节的。小鼠中的 Pmca4 缺失,无论是全身性的还是特异性地成纤维细胞中的缺失,都会降低对压力过载的肥大反应;然而,在心肌细胞中特异性敲除 Pmca4 不会产生这种效果。从机制上讲,缺乏 PMCA4 的心脏成纤维细胞会产生更高水平的分泌型卷曲相关蛋白 2 (sFRP2),从而抑制邻近心肌细胞的肥大反应。此外,我们表明用 PMCA4 抑制剂金精三羧酸 (ATA) 治疗可抑制和逆转由压力超负荷引起的小鼠心脏肥大。